Clostridium difficile infection (CDI) is a significant cause of antibiotic-associated nosocomial diarrhea. While discontinuation of the offending antibiotic is the ideal strategy to control the disease, in most cases, treatment with antimicrobial agents active against C. difficile is deemed necessary because of the severity of the gastrointestinal disease or the presence other active infections. Unfortunately, antimicrobial treatment for a first episode of CDI is associated with up to 25% recurrence of the disease (1).
After one incidence of recurrence, rates increase to up to 60% (2). A recurrence rate of up to almost 50% has been noted with metronidazole use (3). Even in the carrier state, it had been shown that treatment with either metronidazole or vancomycin of individuals with C. difficile is associated with the reisolation of the organism in the stool 2 months later, with recurrence not necessarily coming from the original strain (4). The recent epidemic saw the increasing failure of metronidazole to cure CDI (3, 5, 6). Vancomycin is now the drug of choice for severe disease (1, 7).
Fidaxomicin, a drug newly approved by the FDA, the European Medicines Agency, and Canada Health, is at least as effective as vancomycin in treating acute infection, but has been shown to have less recurrence (8). However, in infections due to NAP1/BI/027, the rates of recurrence in subjects treated with fidaxomicin and vancomycin were similar: 24.4% and 23.6%, respectively. Treatment of recurrent disease is problematic. For the first recurrence, a repetition of the regimen for the initial episode of CDI is recommended. Although there are no solid data for efficacy, prolonged and tapering or pulsed doses of vancomycin are the recommended strategy to treat a second recurrence (1). Even less evidence is available for alternative therapies for succeeding recurrences. Other antibiotics such as nitazoxanide and rifaximin, among others, had been considered (9, 10).
C. difficile infection is the most common cause of antibiotic-associated diarrhea. Unfortunately, antibiotic therapy remains as the standard treatment for this antibiotic-induced disease and relapses are common. Antibiotic treatment typically is given for 10 to 14 days for an initial or second episode of CDI ant at a dose of 2,000 mg/day or more. For recurrent episodes, more prolonged courses are recommended.
Alteration of the indigenous intestinal flora is critical to susceptibility to CDI and its recurrence. Antibiotic treatment may further disrupt the already abnormal flora and thereby enhance the growth of any leftover C. difficile organisms or of a newly acquired strain once antibiotics are discontinued.
There is a long felt need in the art for compositions and methods useful for treating C. difficile infection and for lowering the recurrence rate. The present invention satisfies theses needs.